Pharmacokinetics of rectal levetiracetam as add-on treatment in dogs affected by cluster seizures or status epilepticus

Abstract

BackgroundLevetiracetam can be used for seizure control alone or in combination with other antiepileptic medications. A previous study achieved the minimum targeted serum drug concentration after rectal administration of levetiracetam in healthy dogs. The purpose of the present study was to determine the pharmacokinetics of rectal LEV in dogs presented for cluster seizures or status epilepticus and potentially in treatment with other anti-epileptic drugs. Furthermore, preliminary information on response to this treatment as add-on to the standard treatment protocol is reported.ResultsEight client-owned dogs were enrolled. Plasma levetiracetam concentrations (measured at 0, 30, 60, 90, 120, 180, 240, 360, 720, and 1440 min after drug administration) reached the minimum target concentration (5 μg/ml) at 30 min in all but one patient. At T1 (30 min) the mean concentration was 28.2 ± 15.5 μg/ml. Plasma concentrations remained above the targeted minimum concentration in all patients until 240 min and in 7/8 until 360 min. Six out of eight patients experienced no seizures in the 24-h period after hospitalization and were classified as “responders”.ConclusionsMinimum plasma levetiracetam concentration can be reached after rectal administration of 40 mg/kg in dogs affected by cluster seizures and status epilepticus and concurrently receiving other antiepileptic drugs. These preliminary results may encourage the evaluation of rectal levetiracetam as an additional treatment option for cluster seizures and status epilepticus in a larger number of dogs.Electronic supplementary materialThe online version of this article (10.1186/s12917-018-1522-0) contains supplementary material, which is available to authorized users.

Open‐label clinical trial of rectally administered levetiracetam as supplemental treatment in dogs with cluster seizures

“…The LEV suspension employed was created and administered as previously reported . The dogs were monitored for additional seizures for the first 24 hours after admission and until discharge.…”

“…The pharmacokinetics of LEV after rectal administration in both healthy and epileptic dogs recently has been investigated. These studies indicated that administration of 40 mg/kg per rectum achieved the minimum target concentration of 5 μg/mL 10 and 30 minutes after the administration in healthy and affected dogs, respectively …”

“…Eight dogs included in the present study had been enrolled in a previous study evaluating the pharmacokinetics of LEV administered per rectum in dogs with CS and SE. 12 The LEV suspension employed was created and administered as previously reported. 12 The dogs were monitored for additional seizures for the first 24 hours after admission and until discharge.…”

“…12 The LEV suspension employed was created and administered as previously reported. 12 The dogs were monitored for additional seizures for the first 24 hours after admission and until discharge. Dogs that experienced no additional seizures in the first 24 hours were defined as responders, whereas those that showed additional seizure activity and therefore required other AEMs in the first 24 hours were classified as nonresponders.…”

“…These studies indicated that administration of 40 mg/kg per rectum achieved the minimum target concentration of 5 μg/mL 10 and 30 minutes after the administration in healthy and affected dogs, respectively. 11,12 Our aim was to investigate the clinical efficacy of rectally administered LEV in preventing additional seizures when administered to dogs presented for CS and SE. We hypothesized that administration of LEV rectally in addition to a standard treatment protocol would provide better control of seizure activity as compared with the standard treatment protocol alone.…”